Identity of a differentiation inhibiting factor for mouse myeloid leukemia cells with NM23/nucleoside diphosphate kinase

Okabe‐Kado, Junko; Kasukabe, Takashi; Honma, Yoshio; Hayashi, Moriaki; Henzel, William J.; Hozumi, Motoo

doi:10.1016/0006-291x(92)91829-f

Cited by 108 publications

(49 citation statements)

References 20 publications

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“…18 Serum NDPK-A suggests a secreted form, similar to that reported in myeloid leukemia. 19 Although nm23-H1 mutations are rare, a serine 120 → glycine (S120G) mutation of NDPK-A has been reported in 21% (6 of 28) of advanced neuroblastomas, but not in any of 22 limited-stage tumors. 20 This S120G mutation appears to be specific to neuroblastoma as it was not detected in 26 breast carcinoma patients nor in 17 patients with acute leukemia.…”

Section: Nm23-h1 Genetics and Prognosis Of Neuroblastomamentioning

confidence: 99%

NDPKA is not just a metastasis suppressor – be aware of its metastasis-promoting role in neuroblastoma

Tan

␣Chang

2018

Laboratory Investigation

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NDPK-A, encoded by nm23-H1 (also known as NME1) was the first metastasis suppressor discovered. Much of the attention has been focused on the metastasis-suppressing role of NDPK-A in human tumors, including breast carcinoma and melanoma. However, compelling evidence points to a metastasis-promoting role of NDPK-A in certain tumors such as neuroblastoma and lymphoma. To balance attention on this contrariety of NDPK-A in different cancer types, this review addresses the metastasis-promoting role of NDPK-A in neuroblastoma. Neuroblastoma is an embryonic tumor, arising from neural crest cells that fail to differentiate into the sympathetic nervous system. We summarize and discuss nm23-H1 genetics and the prognosis of neuroblastoma, structural and functional changes associated with the S120G mutation of NDPK-A, as well as the evidence supporting the role of NDPK-A as a metastasis promoter. Also discussed are the NDPK-A relevant molecular determinants of neuroblastoma metastasis, and metastasis-relevant neural crest development. Because of NDPK-A's dichotomous role in tumor metastasis as both a suppressor and a promoter, tumor genome/exome profiles are necessary to identify the molecular drivers of metastasis in the NDPK-A network for developing tumor-specific therapies.

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Section: Nm23-h1 Genetics and Prognosis Of Neuroblastomamentioning

confidence: 99%

NDPKA is not just a metastasis suppressor – be aware of its metastasis-promoting role in neuroblastoma

Tan

␣Chang

2018

Laboratory Investigation

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“…10,11,14 Overexpression of the nm23-H1 and nm23-H2 transcripts in AML cells has been previously described. 13,15 In addition, high nm23-H1 expression level has been correlated with the poor prognosis of AML.…”

Section: Discussionmentioning

confidence: 86%

“…[10][11][12][13][14][15][16] The nm23 proteins are involved in tumor metastasis regulation and have nucleoside diphosphate kinase enzyme activity that catalyzes the ATP-dependent synthesis of nucleoside diphosphates. [17][18][19][20][21][22][23][24] The expression of nm23-H1 has been reported to have an inverse relationship with metastatic potential and in various malignancies.…”

Section: Introductionmentioning

confidence: 99%

Elevated plasma level of differentiation inhibitory factor nm23-H1 protein correlates with risk factors for myelodysplastic syndrome

et al. 2002

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We measured plasma nm23-H1 level (nm23-H1), a differentiation inhibitory factor, by an enzyme-linked immunosorbent assay (ELISA) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). The nm23-H1 in AA was not significantly elevated when compared to normal subjects (6.66 ± 1.20 ng/ml vs 5.13 ± 0.81 ng/ml; P = 0.274). In contrast, MDS patients had significantly high levels of nm23-H1 compared not only to normal subjects (11.16 ± 1.42 vs 5.13 ± 0.81 ng/ml; P = 0.0004) but also to those of the AA group (11.16 ± 1.42 ng/ml vs 6.66 ± 1.20 ng/ml; P = 0.018). In the MDS group of patients, no significant difference was observed in the nm23-H1 levels between patients with refractory anemia (RA) and RA with excess blasts (RAEB)/RAEB in transformation (10.71 ± 1.61 ng/ml vs 9.24 ± 2.66 ng/ml; P = 0.672). Of the patients with RA, patients with low risk according to the International Prognostic Scoring System (IPSS) had significantly low levels of nm23-H1 compared to those of IPSS INT-1 level cases (6.40 ± 1.36 ng/ml vs 13.05 ± 2.50 ng/ml; P = 0.0028), suggesting that nm23-H1 may be useful as a prognostic marker for MDS, especially in low risk patients.

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“…The proteins encoded by nm23-H] and -H2 show 88% amino acid sequence homology and the genes locate on the same region of chromosome 17q21 in tandem (Gilles et al, 1991;Stahl et al, 1991;Backer et al, 1993;Chandrasekharappa et al, 1993;Okada et al, 1994). We found that a differentiation inhibitory factor (I-factor) purified from a differentiation-resistant mouse myeloid leukaemia cell line was identical to the nm23 protein (Okabe-Kado et al, 1992). The nm23-Hl and -H2 proteins inhibited the induction of the differentiation of mouse myelogenous leukaemia M1 and WEHI-3BD+ and human erythroleukaemia HEL, KU812, and K562 cells.…”

mentioning

confidence: 96%

“…Suppression of the production of the inhibitory factors resulted in the non-differentiating leukaemic cells becoming sensitive to differentiation inducers. One of the factors was purified as a homologue of nm23 (Okabe-Kado et al, 1992). …”

mentioning

confidence: 99%

Combined analysis of differentiation inhibitory factor nm23-H1 and nm23-H2 as prognostic factors in acute myeloid leukaemia

Wakimoto

Yokoyama²,

Okabe‐Kado³

et al. 1998

Br J Cancer

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Summary Differentiation inhibitory factor (nm23 protein) inhibited the induction of the differentiation of various leukaemic cell lines. We previously reported that nm23 genes (Hi and H2) were overexpressed in acute myelogenous leukaemia (AML) and nm23-H1 expression predicted the prognosis of AML, especially AML-M5. To clarify the correlation between French-American-British (FAB) classification and nm23 expression level and to clarify the involvement of nm23-H2 and nm23-H1 in patient survival, we investigated the relative levels of nm23-Hi and -H2 mRNA in 76 AML samples using the reverse transcriptase-polymerase chain reaction. We confirmed that the expression of both nm23-Hl and -H2 genes in AML samples from three different hospitals was significantly higher than that in normal blood cells (P < 0.0005). Overexpression of nm23-H1 was observed in each FAB AML-M1, -M2, -M3, -M4 or -M5 subtype, and the predictive effect of nm23-Hl expression on AML prognosis was shown in FAB AML-M2 and -M5 cases. Although overexpression of nm23-H2 was also found in each FAB subtype, the expression of nm23-H2 in AML-M1 and -M3 cells was not significantly higher than that in normal cells. Among AML subtypes, AML-M3 showed the lowest expression levels of both nm23 genes. To understand the relationship between nm23-H1 and -H2 expression levels, nm23 expression levels for all the AML cases were plotted and divided into four groups (group A, nm23-H1 and -H2 both high; B, both low; C, only nm23-Hl high; D, only nm23-H2 high). A statistically significant correlation between the levels of expression of nm23-Hl and -H2 was observed (r= 0.726). Most AML-M3 cases belonged to group B, but not other types of AML. Analysis of survival probability between the groups showed that group B survived for significantly longer compared with group A. Furthermore, AML-M3 cases survived for significantly longer compared with non-M3 cases in the same group B. These data suggest that low expression levels of both nm23-Hl and -H2 are associated with good prognosis in AML patients.Keywords: differentiation inhibitory factor; nm23; acute myelogenous leukaemia; acute promyelocytic leukaemia; prognostic factor The degree of differentiation is an important prognostic factor in leukaemia. For example, patients with leukaemia of the undifferentiated phenotype have a lower response rate to treatment and poor survival. Induction of differentiation is closely linked to loss of leukaemogenicity and blocks expression of the malignant phenotypes. Conversely, a disorder of the cellular differentiation of malignant cells reflects clinical behaviour and therapeutic responses. Normal haematopoiesis can be controlled by various positive and negative regulatory molecules. In myeloid leukaemia, these signals continue to operate, but in an unbalanced fashion, allowing emergence and eventual dominance of a malignant clone. Leukaemic cells are arrested in less differentiated stages of development. These results suggest that negative regulators are also important to regulate different...

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Identity of a differentiation inhibiting factor for mouse myeloid leukemia cells with NM23/nucleoside diphosphate kinase

Cited by 108 publications

References 20 publications

NDPKA is not just a metastasis suppressor – be aware of its metastasis-promoting role in neuroblastoma

NDPKA is not just a metastasis suppressor – be aware of its metastasis-promoting role in neuroblastoma

Elevated plasma level of differentiation inhibitory factor nm23-H1 protein correlates with risk factors for myelodysplastic syndrome

Combined analysis of differentiation inhibitory factor nm23-H1 and nm23-H2 as prognostic factors in acute myeloid leukaemia

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